Enhanced method performances for conventional and chiral CE-ESI/MS analyses in plasma

Area of Science:

• Analytical Chemistry
• Biomedical Analysis
• Mass Spectrometry

Background:

• Capillary electrophoresis-electrospray ionization/mass spectrometry (CE-ESI/MS) is highly efficient for drug and metabolite analysis in biological samples.
• Effective sample preparation is crucial for successful CE-ESI/MS analysis.
• Understanding matrix effects is essential for reliable results in complex biological samples.

Purpose of the Study:

• To develop fast and simplified sample preparation methods for plasma samples prior to CE-ESI/MS analysis.
• To compare protein precipitation (PP) and liquid-liquid extraction (LLE) combined with hydrodynamic (HD) and electrokinetic (EK) injection techniques.
• To investigate matrix effects in CE-ESI/MS using different sample preparation methods.

Main Methods:

• Developed CE-ESI/MS methods for pharmaceutical compounds and amphetamine derivatives.
• Employed protein precipitation (PP) and liquid-liquid extraction (LLE) for sample preparation.
• Utilized hydrodynamic (HD) and electrokinetic (EK) injection techniques.
• Investigated stereoselective determinations using partial-filling mode.
• Assessed matrix effects using a coaxial sheath-liquid ESI interface.

Main Results:

• Detection limits of 1 ppm were achieved with PP and HD injection.
• Detection limits of 1 ppb were achieved with LLE and EK injection.
• Stereoselective determinations yielded detection limits of 0.5 ppb per enantiomer.
• Matrix effects were observed with PP, causing signal suppression outside the migration window.
• LLE demonstrated no significant matrix effects across all experiments.

Conclusions:

• Liquid-liquid extraction combined with electrokinetic injection provides superior sensitivity and minimal matrix effects for CE-ESI/MS analysis of plasma samples.
• Protein precipitation can lead to matrix effects that may compromise results.
• The developed CE-ESI/MS methods are suitable for both routine drug analysis and stereoselective determinations.